Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

6.3K
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.3K
Combined Effects of Drugs: Synergism01:27

Combined Effects of Drugs: Synergism

3.8K
Synergism is a useful mechanism where combining two or more drugs is more effective than each constituent used alone. Such combinations are also called supra-additive interactions. The drugs collectively enhance the final therapeutic effect by acting on different targets. Another advantage is that the low dose of each constituent drug is sufficient to achieve the desired effect. This helps reduce the duration of therapy and lower the adverse effects of these drugs.
Such synergistic combinations...
3.8K
Nonlinear Pharmacokinetics: Dependence of Elimination Half-Life and Dose Clearance01:23

Nonlinear Pharmacokinetics: Dependence of Elimination Half-Life and Dose Clearance

115
The elimination half-life and drug clearance of drugs following nonlinear kinetics can vary with dosage. The Michaelis-Menten parameters and drug concentration influence these factors. As the dose increases, the elimination half-life tends to lengthen, resulting in a reduction in clearance and a disproportionately larger area under the curve. The total clearance can be derived from the Michaelis-Menten equation for drugs following a one-compartment model.
A study on guinea pigs examined the...
115
Lipid-Lowering Drugs: Statins and Miscellaneous Agents01:20

Lipid-Lowering Drugs: Statins and Miscellaneous Agents

621
Hyperlipidemia, a medical condition often referred to as high cholesterol, is characterized by abnormally elevated levels of lipids in the bloodstream. When present in excess, these lipids, specifically cholesterol and triglycerides, can lead to serious health complications, often involving cardiovascular diseases. Illnesses like atherosclerosis, heart attacks, and pancreatitis have all been linked to untreated hyperlipidemia. This means controlling and regulating cholesterol and triglyceride...
621
Feedback Inhibition00:46

Feedback Inhibition

53.8K
Biochemical reactions are occurring constantly in cells, converting starting substances to different products, usually with the help of enzymes that speed the reactions. Without enzymes, it would take far too long for most reactions to occur to be useful to the cell!
53.8K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

4.7K
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.7K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Comparison of Common Plasma Proteomics Workflows Reveals Distinct Preanalytical Biases by Sample Preparation and Nanoparticle Enrichment.

Journal of proteome research·2026
Same author

Identification of novel drug-specific PARP inhibitor resistance mechanisms in ovarian cancer-implications for clinical practice.

British journal of cancer·2026
Same author

Systematic analyses of lipid mobilization by human lipid transfer proteins.

Nature·2026
Same author

In silico biological discovery with large perturbation models.

Nature computational science·2025
Same author

Impact of Local Air Pressure on Ion Mobilities and Data Consistency in diaPASEF-Based High Throughput Proteomics.

Journal of proteome research·2025
Same author

PeptideForest: Semisupervised Machine Learning Integrating Multiple Search Engines for Peptide Identification.

Journal of proteome research·2025

Related Experiment Video

Updated: Jun 20, 2025

Laser Microirradiation to Study In Vivo Cellular Responses to Simple and Complex DNA Damage
10:44

Laser Microirradiation to Study In Vivo Cellular Responses to Simple and Complex DNA Damage

Published on: January 31, 2018

10.2K

Synergistic Effects of PARP Inhibition and Cholesterol Biosynthesis Pathway Modulation.

Anna Rutkowska1, H Christian Eberl1, Thilo Werner1

  • 1Cellzome, GSK, R&D, Heidelberg, Germany.

Cancer Research Communications
|July 19, 2024
PubMed
Summary

Niraparib uniquely targets lanosterol synthase, impacting cholesterol biosynthesis. Combining PARP inhibitors with cholesterol pathway modulators like statins shows synergistic cancer cell killing, suggesting a new therapeutic strategy.

More Related Videos

Cell Death Associated with Abnormal Mitosis Observed by Confocal Imaging in Live Cancer Cells
15:53

Cell Death Associated with Abnormal Mitosis Observed by Confocal Imaging in Live Cancer Cells

Published on: August 21, 2013

14.9K
LDL Cholesterol Uptake Assay Using Live Cell Imaging Analysis with Cell Health Monitoring
08:45

LDL Cholesterol Uptake Assay Using Live Cell Imaging Analysis with Cell Health Monitoring

Published on: November 17, 2018

13.3K

Related Experiment Videos

Last Updated: Jun 20, 2025

Laser Microirradiation to Study In Vivo Cellular Responses to Simple and Complex DNA Damage
10:44

Laser Microirradiation to Study In Vivo Cellular Responses to Simple and Complex DNA Damage

Published on: January 31, 2018

10.2K
Cell Death Associated with Abnormal Mitosis Observed by Confocal Imaging in Live Cancer Cells
15:53

Cell Death Associated with Abnormal Mitosis Observed by Confocal Imaging in Live Cancer Cells

Published on: August 21, 2013

14.9K
LDL Cholesterol Uptake Assay Using Live Cell Imaging Analysis with Cell Health Monitoring
08:45

LDL Cholesterol Uptake Assay Using Live Cell Imaging Analysis with Cell Health Monitoring

Published on: November 17, 2018

13.3K

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Poly (ADP-ribose) polymerase (PARP) inhibitors are crucial in cancer therapy.
  • Niraparib exhibits unique poly-pharmacology not seen in other PARP inhibitors.
  • Cholesterol biosynthesis is implicated in various cancer types.

Purpose of the Study:

  • To investigate the molecular mechanisms of niraparib's poly-pharmacology.
  • To explore the therapeutic potential of combining PARP inhibitors with cholesterol biosynthesis pathway modulators.

Main Methods:

  • Multiomic molecular characterization of PARP inhibitors.
  • In vitro studies using cancer cell lines and patient-derived ovarian tumor organoids.
  • Pharmacological inhibition of lanosterol synthase (LSS) and 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR).

Main Results:

  • Niraparib interacts with lanosterol synthase (LSS), activating the 24,25-epoxysterol shunt pathway.
  • Combination of LSS inhibitors with non-LSS binding PARP inhibitors (e.g., olaparib) showed additive cancer cell killing.
  • Concomitant inhibition of PARP and cholesterol biosynthesis (using statins) demonstrated synergistic tumor cell killing.

Conclusions:

  • Niraparib's unique interaction with LSS offers a distinct therapeutic approach.
  • Combined inhibition of PARP and cholesterol biosynthesis pathways presents a promising strategy for enhanced anti-tumor efficacy.
  • Further investigation is warranted to assess the translational relevance of these findings.